title: Odour receptors and neurons for DEET and new insect repellents.
abstract: There are major impediments to finding improved DEET alternatives because the receptors causing olfactory repellency are unknown, and new chemicals require exorbitant costs to determine safety for human use. Here we identify DEET-sensitive neurons in a pit-like structure in the Drosophila melanogaster antenna called the sacculus. They express a highly conserved receptor, Ir40a, and flies in which these neurons are silenced or Ir40a is knocked down lose avoidance to DEET. We used a computational structure-activity screen of >400,000 compounds that identified >100 natural compounds as candidate repellents. We tested several and found that most activate Ir40a(+) neurons and are repellents for Drosophila. These compounds are also strong repellents for mosquitoes. The candidates contain chemicals that do not dissolve plastic, are affordable and smell mildly like grapes, with three considered safe in human foods. Our findings pave the way to discover new generations of repellents that will help fight deadly insect-borne diseases worldwide.
authors.affiliation: 1] Department of Entomology, University of California, Riverside, California 92521, USA [2].
authors.forename: Pinky
authors.initials: P
authors.lastname: Kain
authors.forename: Sean Michael
authors.initials: SM
authors.lastname: Boyle
authors.forename: Sana Khalid
authors.initials: SK
authors.lastname: Tharadra
authors.forename: Tom
authors.initials: T
authors.lastname: Guda
authors.forename: Christine
authors.initials: C
authors.lastname: Pham
authors.forename: Anupama
authors.initials: A
authors.lastname: Dahanukar
authors.forename: Anandasankar
authors.initials: A
authors.lastname: Ray
mesh_terms: D000818:Animals; D057506:Arthropod Antennae / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001362:Avoidance Learning / Q000187:drug effects; D003198:Computer Simulation; D009033:Culicidae / Q000187:drug effects / Q000502:physiology; D003671:DEET / Q000378:metabolism* / Q000494:pharmacology; D004331:Drosophila melanogaster / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007302:Insect Repellents / Q000009:adverse effects / Q000378:metabolism* / Q000494:pharmacology; D018035:Receptors, Odorant / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*
chemical_list: D007302:Insect Repellents; D018035:Receptors, Odorant; D003671:DEET